The papillomavirus E2 protein is a key regulator of viral life cycle, controlling several important functions. It stimulates replication by cooperatively binding the viral origin of replication with the viral helicase E1. It activates transcription from many viral promoters, regulating levels of the oncoproteins E6 and E7 among others. Finally, it appears to be involved in tethering the viral genome to the host cell chromosomes to ensure faithful segregation during mitosis. Residues crucial for each of these functions have been mapped to the N-terminal activation domain of about 200 amino acids. Evidently then, the structure of this region is full of potential insights into the protein's function, particularly since there have been no isolated eukaryote activation domain structures solved. Last year's work under this proposal allowed us to solve a 144 amino acid piece of the activation domain, leading to new ideas on the protein's key features and corresponding mutagenesis studies. We also have crystals of a construct encompassing the full activation domain and would like to extend our studies on this variant. The crystals are of a long needle/rod morphology that benefits from a strong X-ray source such as a synchrotron. We have shown that these will diffract to at least 2.3 E on a synchrotron with relatively long exposure times. We aim to solve the structure of this longer construct.